Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis.

BACKGROUND: Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, affect more than a third of the world's population, with varying intensity of infection. We aimed to evaluate the effects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or co-interventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse effects in children in endemic helminth areas. METHODS: We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before-after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted random-effects meta-analysis and Bayesian network meta-analysis. FINDINGS: We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8-10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] -0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI -0·10 to 0·24; moderate certainty evidence), little to no difference in proportion stunted (eight fewer per 1000 children, 95% CrI -48 to 32; high certainty evidence), cognition measured by short-term attention (-0·23 points on a 100 point scale, 95% CI -0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI -1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI -3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI -0·20 to 0·91) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefits for untreated children from being exposed to treated children in the community. We are uncertain about effects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. INTERPRETATION: Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little effect. For schistosomiasis, mass deworming might be effective for weight but is probably ineffective for height, cognition, and attendance. Future research should assess which subset of children do benefit from mass deworming, if any, using individual participant data meta-analysis. FUNDING: Canadian Institutes of Health Research and WHO.

Intravenous Vitamin C and Cancer: A Systematic Review.

BACKGROUND: Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients. METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human studies examining the safety, effectiveness, or pharmacokinetics of IVC use in cancer patients. RESULTS: Of 897 records, a total of 39 reports of 37 studies were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6 observational studies, and 14 case reports. IVC dosing ranged from 1 g to more than 200 g ascorbic acid per infusion, typically administered 2 to 3 times weekly. IVC does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on 1 RCT and data from uncontrolled human trials, IVC may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression. Case reports document several instances of tumor regression and long-term disease-free survival associated with use of IVC. CONCLUSION: There is limited high-quality clinical evidence on the safety and effectiveness of IVC. The existing evidence is preliminary and cannot be considered conclusive but is suggestive of a good safety profile and potentially important antitumor activity; however, more rigorous evidence is needed to conclusively demonstrate these effects. IVC may improve the quality of life and symptom severity of patients with cancer, and several cases of cancer remission have been reported. Well-designed, controlled studies of IVC therapy are needed.

Black cohosh and breast cancer: a systematic review.

BACKGROUND: Many women use black cohosh as a natural treatment for menopausal symptoms. However, controversy exists around safety in breast cancer, because of its purported estrogenic activity. We conducted a systematic review of black cohosh use in women with or at risk of breast cancer. METHODS: We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to July 2012 and October 2012 for human interventional or observational data pertaining to the safety and efficacy of black cohosh in patients with or at risk of breast cancer, including an assessment of the effect of black cohosh on estrogen responsive tissues. RESULTS: Of 450 records, we included 26 articles: 14 randomized controlled trials, 7 uncontrolled trials, and 5 observational studies.The evidence on efficacy for ho t flashes is divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas 2 studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), and risk of recurrence (adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89). Seventeen trials showed no significant impact on circulating hormone levels or proliferation in estrogen responsive tissues. CONCLUSIONS: Current evidence does not support an association between black cohosh and increased risk of breast cancer. There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients. Given conflicting but promising results, and apparent safety, further research is warranted.

American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee.

OBJECTIVE: To update the American College of Rheumatology (ACR) 2000 recommendations for hip and knee osteoarthritis (OA) and develop new recommendations for hand OA. METHODS: A list of pharmacologic and nonpharmacologic modalities commonly used to manage knee, hip, and hand OA as well as clinical scenarios representing patients with symptomatic hand, hip, and knee OA were generated. Systematic evidence-based literature reviews were conducted by a working group at the Institute of Population Health, University of Ottawa, and updated by ACR staff to include additions to bibliographic databases through December 31, 2010. The Grading of Recommendations Assessment, Development and Evaluation approach, a formal process to rate scientific evidence and to develop recommendations that are as evidence based as possible, was used by a Technical Expert Panel comprised of various stakeholders to formulate the recommendations for the use of nonpharmacologic and pharmacologic modalities for OA of the hand, hip, and knee. RESULTS: Both "strong" and "conditional" recommendations were made for OA management. Modalities conditionally recommended for the management of hand OA include instruction in joint protection techniques, provision of assistive devices, use of thermal modalities and trapeziometacarpal joint splints, and use of oral and topical nonsteroidal antiinflammatory drugs (NSAIDs), tramadol, and topical capsaicin. Nonpharmacologic modalities strongly recommended for the management of knee OA were aerobic, aquatic, and/or resistance exercises as well as weight loss for overweight patients. Nonpharmacologic modalities conditionally recommended for knee OA included medial wedge insoles for valgus knee OA, subtalar strapped lateral insoles for varus knee OA, medially directed patellar taping, manual therapy, walking aids, thermal agents, tai chi, self management programs, and psychosocial interventions. Pharmacologic modalities conditionally recommended for the initial management of patients with knee OA included acetaminophen, oral and topical NSAIDs, tramadol, and intraarticular corticosteroid injections; intraarticular hyaluronate injections, duloxetine, and opioids were conditionally recommended in patients who had an inadequate response to initial therapy. Opioid analgesics were strongly recommended in patients who were either not willing to undergo or had contraindications for total joint arthroplasty after having failed medical therapy. Recommendations for hip OA were similar to those for the management of knee OA. CONCLUSION: These recommendations are based on the consensus judgment of clinical experts from a wide range of disciplines, informed by available evidence, balancing the benefits and harms of both nonpharmacologic and pharmacologic modalities, and incorporating their preferences and values. It is hoped that these recommendations will be utilized by health care providers involved in the management of patients with OA.

Teaching evidence-based complementary and alternative medicine: 3. Asking the questions and identifying the information.

Practicing evidence-based complementary and alternative medicine (EBCAM) requires skills in accessing current valid literature on clinical queries. This requires searching a variety of sources within a broad scope of scientific disciplines. This daunting task requires effective skills for accessing information from both print and electronic sources. This paper identifies the progression from question formulation through to searching and acquiring the valid information. In the evolving information age, complementary and alternative medicine (CAM) practitioners require informational databases and knowledge of search terminology. This paper suggests practical strategies for successful database searches in support of EBCAM.

Teaching evidence-based complementary and alternative medicine: 5. Interpreting the results of a study on therapy and applying them to a patient.

Practicing evidence-based complementary and alternative medicine (CAM) requires that practitioners develop an ability to understand and appropriately apply the results of published studies addressing questions related to their clinical practice. This paper describes a process by which CAM practitioners can interpret the results of studies evaluating therapeutic interventions and then determine if they can apply these results to their patients. We describe a process for interpreting the results of a study on therapy that involves determining the estimate of the magnitude of the therapy's effect and determining the precision of this estimate. We then describe a process for determining whether the results of a study on therapy can be applied to a given patient that involves determining the extent to which patients in the study differ from the patient being treated and determining if the study addressed all outcomes of interest.